Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Aging (Upcoming)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • Circadian Rhythm (Oct 2021)
    • Gut-Brain Axis (Jul 2021)
    • Tumor Microenvironment (Mar 2021)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a comment
  • Share this article
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal
  • Top
  • Version history
  • Article usage
  • Citations to this article

Advertisement

Erratum Free access | 10.1172/JCI62856

Alkylpurine–DNA–N-glycosylase confers resistance to temozolomide in xenograft models of glioblastoma multiforme and is associated with poor survival in patients

Sameer Agnihotri, Aaron S. Gajadhar, Christian Ternamian, Thierry Gorlia, Kristin L. Diefes, Paul S. Mischel, Joanna Kelly, Gail McGown, Mary Thorncroft, Brett L. Carlson, Jann N. Sarkaria, Geoffrey P. Margison, Kenneth Aldape, Cynthia Hawkins, Monika Hegi, and Abhijit Guha

Find articles by Agnihotri, S. in: JCI | PubMed | Google Scholar

Find articles by Gajadhar, A. in: JCI | PubMed | Google Scholar

Find articles by Ternamian, C. in: JCI | PubMed | Google Scholar

Find articles by Gorlia, T. in: JCI | PubMed | Google Scholar

Find articles by Diefes, K. in: JCI | PubMed | Google Scholar

Find articles by Mischel, P. in: JCI | PubMed | Google Scholar

Find articles by Kelly, J. in: JCI | PubMed | Google Scholar

Find articles by McGown, G. in: JCI | PubMed | Google Scholar

Find articles by Thorncroft, M. in: JCI | PubMed | Google Scholar

Find articles by Carlson, B. in: JCI | PubMed | Google Scholar

Find articles by Sarkaria, J. in: JCI | PubMed | Google Scholar

Find articles by Margison, G. in: JCI | PubMed | Google Scholar

Find articles by Aldape, K. in: JCI | PubMed | Google Scholar

Find articles by Hawkins, C. in: JCI | PubMed | Google Scholar

Find articles by Hegi, M. in: JCI | PubMed | Google Scholar

Find articles by Guha, A. in: JCI | PubMed | Google Scholar

Published February 1, 2012 - More info

Published in Volume 122, Issue 2 on February 1, 2012
J Clin Invest. 2012;122(2):782–782. https://doi.org/10.1172/JCI62856.
© 2012 The American Society for Clinical Investigation
Published February 1, 2012 - Version history
View PDF

Related article:

Alkylpurine–DNA–N-glycosylase confers resistance to temozolomide in xenograft models of glioblastoma multiforme and is associated with poor survival in patients
Sameer Agnihotri, … , Monika Hegi, Abhijit Guha
Sameer Agnihotri, … , Monika Hegi, Abhijit Guha
Research Article Oncology

Alkylpurine–DNA–N-glycosylase confers resistance to temozolomide in xenograft models of glioblastoma multiforme and is associated with poor survival in patients

  • Text
  • PDF
Abstract

Glioblastoma multiforme (GBM) is the most common and lethal of all gliomas. The current standard of care includes surgery followed by concomitant radiation and chemotherapy with the DNA alkylating agent temozolomide (TMZ). O6-methylguanine–DNA methyltransferase (MGMT) repairs the most cytotoxic of lesions generated by TMZ, O6-methylguanine. Methylation of the MGMT promoter in GBM correlates with increased therapeutic sensitivity to alkylating agent therapy. However, several aspects of TMZ sensitivity are not explained by MGMT promoter methylation. Here, we investigated our hypothesis that the base excision repair enzyme alkylpurine–DNA–N-glycosylase (APNG), which repairs the cytotoxic lesions N3-methyladenine and N7-methylguanine, may contribute to TMZ resistance. Silencing of APNG in established and primary TMZ-resistant GBM cell lines endogenously expressing MGMT and APNG attenuated repair of TMZ-induced DNA damage and enhanced apoptosis. Reintroducing expression of APNG in TMZ-sensitive GBM lines conferred resistance to TMZ in vitro and in orthotopic xenograft mouse models. In addition, resistance was enhanced with coexpression of MGMT. Evaluation of APNG protein levels in several clinical datasets demonstrated that in patients, high nuclear APNG expression correlated with poorer overall survival compared with patients lacking APNG expression. Loss of APNG expression in a subset of patients was also associated with increased APNG promoter methylation. Collectively, our data demonstrate that APNG contributes to TMZ resistance in GBM and may be useful in the diagnosis and treatment of the disease.

Authors

Sameer Agnihotri, Aaron S. Gajadhar, Christian Ternamian, Thierry Gorlia, Kristin L. Diefes, Paul S. Mischel, Joanna Kelly, Gail McGown, Mary Thorncroft, Brett L. Carlson, Jann N. Sarkaria, Geoffrey P. Margison, Kenneth Aldape, Cynthia Hawkins, Monika Hegi, Abhijit Guha

×

Original citation: J. Clin. Invest. 2012;122(1):253–266. doi:10.1172/JCI59334.

Citation for this erratum: J. Clin. Invest. 2012;122(2):782. doi:10.1172/JCI62856.

During the preparation of this manuscript, Figure 8B was inadvertently mislabeled. The correct figure appears below.

Figure 8

The JCI regrets the error.

Version history
  • Version 1 (February 1, 2012): No description

Article tools

  • View PDF
  • Download citation information
  • Send a comment
  • Share this article
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal

Metrics

  • Article usage
  • Citations to this article

Go to

  • Top
  • Version history
Advertisement
Advertisement

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts